The overall objective of the research is to elucidate both the nature and possible interrelation of conditioned analgesia (CA) and conditioned immunomodulation (CIM). Aims in the area of CA are to: (1) determine the time course and opiate or nonopiate of the analgesic reaction (AK) that is generated, not only by the conditioned stimulus that signals a shock unconditioned stimulus (US), but also by the US itself and by the compound of the CS and us; (2) evaluate whether the enhanced opiate AR that has been deducted for the CS/US compound underlies other aversive- conditioning phenomena, such as "blocking," the US-preexposure effect, and the preference for signaled over unsignaled shock; and (3) assess whether opiate for related) mechanisms are involved in appetitive (Ap), as well as aversive (Av), conditioning, as is suggested by the functional similarity of Ap and Av CSs of opposite sign, e.g., a CS- signaling the absence of food and a CS+ signaling the presence of shock. In the area of CIM, our aims are to: (1) determine whether that phenomenon, as shown in the immunosuppression produced by a CS+ for shook is mediated by endogenous opiates and/or a general anxiety reaction; (2) assess whether CIM is akin to other Av conditioning phenomena and generates "standard" effects, such contextual conditioning, US preexposure, and blocking; (3) evaluate whether CIM is subject to higher-order conditioning and whether that effect functions independently of first-order CS+ and affects the same or different immune compartments; (4) determine whether a CS- that inhibits fear by signaling the absence of shock can attenuate the munosuppresion produced by a CS+ for shock or, on its own, enhance immune function; (5) conduct similar evaluations of other ameliorative procedures, such as training with a ApCS+, a signal thought to elicit the emotional reaction of "hope"; and (6) investigate whether immunization itself affects the conditioning process. Where appropriate, the search will employ an Av conditioning method that assesses the suppression of a baseline response and an Ap conditioning technique that evaluates the latency of a food- directed response. Analgesic reactions will be measured by thermal-sensitivity tests, and immune function assayed by both in vitro and in vivo tests. The significance of the research lies not only in enhancing our knowledge of the conditioning process, but also in documenting that psychological stress in the form of conditioned fear or frustration can modulate pain sensitivity and immunocompetence. That, in turn, can foster the development of clinically relevant psychological practices for reducing pain and immune dysfunction.